Management of Patients With Thoracic Aortic Aneurysm: A Challenging Problem for the Clinician

Thoracic aortic aneurysm (TAA) is a dangerous and silent disease that is difficult to diagnose in the initial stage before complications develop.1,2 The natural history of a TAA is to enlarge over time increasing the risk for an acute thoracic aortic rupture/dissection.3,4 Average growth rate of TAAs ranges from 0.2 to 4.2 mm/year.4 Both environmental and genetic factors play a role in increasing the risk of development of thoracic aortic disease and its complications.5,6 Several lines of research suggest that high hemodynamic load on a structurally defective aorta is the primary cause of TAA.6–9 Factors that heighten biomechanical forces of the pulsatile blood, such as heavy resistance exercise, smoking, cocaine abuse, or pregnancy, increase the risk of TAA.10,11 However, hypertension is unanimously considered to represent the main hemodynamic risk factor for the onset of aortic disease and for its complications.1,11 Accurate measurement of blood pressure (BP) to detect hypertension at an early stage is thus of primary importance in patients with TAA and appropriate strategies should be adopted to achieve this goal (Table 1). Out-of-office BP measurement, especially 24-hour ambulatory monitoring, should be implemented with the main aim of detecting masked hypertension.12 Although out-of-office measurement can refine the assessment of patients with TAA, it should be borne in mind that peripheral BP may not be indicative of central BP measured at the aortic arch. In humans, BP differs according to the measuring site and a well-known phenomenon is the peripheral pulse amplification.13,14 Due to arterial wall stiffness and early pressure wave reflection, BP levels and waveforms significantly differ between central and peripheral arteries with systolic BP and pulse pressure being typically higher and diastolic BP lower in the peripheral sites than in the aorta.13,15 However, these discrepancies may vary from subject to subject and cannot be accurately predicted on the basis of individual patient factors. This highlights the importance of acquiring a reliable estimate of aortic BP in patients with TAA, as central BP might be a better predictor of TAA size and growth than peripheral brachial BP. BP management of patients with thoracic aortic aneurysm Abbreviations: BP, blood pressure; RAS, renin–angiotensin system. BP management of patients with thoracic aortic aneurysm Abbreviations: BP, blood pressure; RAS, renin–angiotensin system. This issue was addressed by Rooprai et al. in 105 patients with TAA defined as an aortic root and/or ascending and/or descending aorta ≥40 mm.16 The main purpose was to evaluate the prevalence of central hypertension in the patients without a diagnosis of brachial hypertension according to oscillometric BP measurement, and to assess the predictive value of central vs. brachial BP for aneurysm size and growth. Central BP was measured with applanation tonometry of the brachial and carotid arteries. Among participants without a diagnosis of brachial hypertension, 15% exhibited central hypertension at applanation tonometry. In these patients, aneurysm size was comparable to that of the patients who carried a diagnosis of brachial hypertension. In addition, TAA growth during a 2.9-year follow-up was greater not only among the participants with both elevated brachial and central BP, but also among those with isolated central hypertension when compared with the participants with normal brachial and central BP. The better clinical value of central BP was confirmed by the results of a multiple regression analysis in the individuals without known hypertension. In this group, central systolic BP and pulse pressure were independently associated with larger TAA size at baseline and faster TAA growth, while brachial BP components were not. Finally, among the participants with known hypertension, central but not brachial BP was associated with greater TAA growth. Overall, the results of this study suggest that central BP measured with applanation tonometry has a greater prognostic value than peripheral BP and that measurement of central BP should thus be included in the current assessment of the patient with TAA. TAA is defined as an aorta diameter greater than 1.5 times the expected size by most scientific societies.17 However, aortic size alone may not distinguish between different pathological processes which imply a different risk of acute complications. Indeed, results of epidemiological studies have shown that acute aortic dissection can occur when the aortic size is below intervention criteria.3,9,17 This highlights the importance of documenting precisely the hemodynamic load exerted on the aorta which can be obtained with central BP measurement. Limiting hemodynamic forces, and in particular controlling central hypertension, would be of paramount importance for preventing the disastrous consequences of TAA growth. However, it should be noted that the reliability of current techniques to measure central BP has been the subject of much debate.15 Intra-arterial measurement remains the gold standard reference for central BP assessment but has the obvious limitation related to the invasive nature of this technique. Several methods for noninvasive central BP measurement are now available.18 The tonometric approach, use by Rooprai et al. in the present study, involves the application of a high-fidelity tonometer to the artery in order to form a flat interface.15 This requires an adequate operator expertise in order to obtain reliable signals. In addition, it should be pointed out that the registered pressure waveform has to be calibrated with conventional (usually oscillometric) brachial BP measurements. As a consequence, the accuracy of peripheral BP measurements remains a major source of uncertainty in noninvasive central BP estimation.19 Indeed, noninvasive estimation of central systolic BP by peripheral tonometric measurements has shown large variability for prediction of invasive BP.19 Another important issue with the use of central BP is the lack of official threshold values that differentiate normal from high central BP. In the present study, the authors used a systolic BP >130 mm Hg to identify central hypertension.16 However, the criteria used to define central hypertension have been highly debated because BP amplification is heavily dependent on age.15 Analysis of cross-sectional data in healthy subjects suggested a cut point of 125/90 mm Hg between normal and high central BP.15 A subsequent study identified the values of 110/80 mm Hg for optimal central BP and of 130/90 mm Hg for hypertension in a derivation cohort.15 Using these thresholds in a validation cohort, the risk of cardiovascular mortality increased significantly in subjects with hypertension compared with those with optimal central BP. However, as mentioned above, the pronounced effect that age has on BP amplification limits the validity of this approach, particularly when trying to establish the threshold levels in the young. Reference values for central systolic BP and pulse pressure have been identified in healthy populations and patients with cardiovascular risk factors, providing age- and gender-specific reference ranges.20 Although this approach looks like a straightforward strategy, it should be pointed out that it has never been applied to identify threshold values of peripheral BP. A possible limitation of the Rooprai et al. study16 is that the diagnosis of hypertension was based on anamnestic information obtained from patients already on antihypertensive treatment and not from actual BP measurements. In addition, 16% of the participants classified as nonhypertensive actually had a BP in the hypertensive range at baseline evaluation but could not be included in the hypertensive group because they had been evaluated on only a single visit. Another limitation, admitted by the authors themselves, is that out-of-office BP was not measured. Ambulatory BP at baseline would have provided complementary prognostic information and have reduced the advantage of central BP assessment. Finally, a clinical aspect not considered by the authors was the role of visit-to-visit BP variability in affecting TAA size and growth. In a recent study by Song et al., BP variability proved to be an independent risk factor for acute type B aortic dissection.21 Hypertensive patients may be especially vulnerable to swings of pressure but little information is available about the prognostic significance of BP variability in patients with TAA. To fully acquire clinical relevance in patients with TAA, longitudinal studies in larger samples will be required to verify the long-term predictive value of noninvasive central hemodynamics on clinical outcomes. TAA patients who undergo assessment of central hemodynamic indices can subsequently be monitored to investigate the relationship between TAA evolution and changes in central hemodynamics. In this respect, it would be productive to standardize the diagnostic protocol and the follow-up, that besides routine clinical assessment and imaging should include careful out-of-office BP assessment and measurement of central BP. Treatment with β-blockers and renin–angiotensin system inhibitors dramatically decreased deaths from aortic dissection in patients with TAA.9,22 However, it has been demonstrated that central and brachial BP can be differently affected by antihypertensive therapy.23 It is thus conceivable that changes of central BP could predict cardiovascular outcomes and mortality better than do changes of brachial BP. Careful control of central BP over time with medical therapy may prove to be the game-changer in the management of TAA. Whether it would be better not only to lower the mean central BP level but also to achieve a more stable BP is a matter for further research. No funds were received for this article. The author declared no conflict of interest.